Atriplex halimus is a medicinal plant traditionally used for various therapeutic purposes. This study evaluated the antioxidant, anti-inflammatory, cytotoxic, genotoxic, and anti-arthritic activities of the A. halimus aqueous extract (AHA). Anti-arthritic effects were investigated in Complete Freund’s Adjuvant (CFA)-induced arthritic rats treated with AHA (150 or 300 mg/kg) for 21 days. AHA significantly reduced paw swelling and arthritis severity and improved body weight, while a non-significant reduction in spleen enlargement was observed. Hematological and biochemical parameters were restored toward normal values, indicating anti-inflammatory, hepatoprotective, and nephroprotective effects. The extract also reduced oxidative stress by decreasing nitric oxide (NO) and malondialdehyde (MDA) levels and increasing glutathione (GSH) content and catalase (CAT) activity. Histopathological examination confirmed reduced inflammatory infiltration and protection against bone damage. Phytochemical analysis revealed polyphenols, flavonoids, and tannins, consistent with its antioxidant activity in DPPH, ABTS, CUPRAC, and o-phenanthroline assays. AHA also showed anti-inflammatory activity by inhibiting bovine serum albumin denaturation. The extract induced a moderate concentration-dependent reduction in HeLa cell viability without cytotoxicity toward HaCaT cells. Comet assay results demonstrated DNA damage in HeLa cells at higher concentrations, while AHA significantly suppressed zymosan-induced IL-1β gene expression. These findings indicate that AHA is a promising natural source of bioactive compounds with diverse biological activities.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation, oxidative stress, and progressive joint destruction. Given the limitations and adverse effects of current therapies, medicinal plants represent a valuable source of novel anti-inflammatory agents. This study evaluated the phytochemical composition, antioxidant, immunomodulatory, and anti-arthritic activities of an ethanolic extract of Urtica urens (UUEE). LC-ESI-HRMS analysis identified forty metabolites, mainly hydroxycinnamic acid derivatives, flavonoids, terpenoid glycosides, and oxidized fatty acids. Antioxidant activity was assessed using DPPH, ABTS, and CUPRAC assays together with total phenolic and flavonoid contents. Anti-arthritic activity was investigated by inhibition of heat-induced bovine serum albumin denaturation, while cytotoxicity and genotoxicity were evaluated in HeLa and HaCaT cells. Immunomodulatory activity was assessed by analyzing IL-6 and IL-1β expression in zymosan-stimulated HaCaT cells. Therapeutic efficacy was validated in a Freund’s complete adjuvant-induced arthritis model in Wistar rats. UUEE showed strong antioxidant activity, concentration-dependent inhibition of protein denaturation, low cytotoxicity up to 100 μg/mL, downregulation of pro-inflammatory cytokines, and significant in vivo anti-arthritic effects, reducing oxidative stress, histopathological damage, and arthritis severity while improving hematological and biochemical parameters. These findings support U. urens as a promising source of bioactive compounds for RA management.

Urtica urens L. (Urticaceae) is a traditional medicinal plant widely used in ethnopharmacology for its pharmacological properties. This study aimed to investigate the LC-MS/MS phenolic profile, antioxidant activity, and cytotoxic potential of the ethyl acetate extract (EAE) from its leaves. Phytochemical characterisation revealed a chemically rich extract dominated by carvacrol, epigallocatechin derivatives, and emodin, along with phenolic acids (ferulic, sinapic, gallic, p-coumaric, and chlorogenic acids), catechin/epicatechin, epigallocatechin gallate, rutin, neohesperidin, isorhamnetin-type flavonoids, and β-sterol. Antioxidant activity was assessed using DPPH^• and ^•OH scavenging assays, showing significant activity with IC₅₀ values of 0.19 ± 0.005 mg/mL and 0.753 ± 0.004 mg/mL, respectively. Cytotoxic effects evaluated by the MTT assay demonstrated notable activity, particularly against MDA-MB-231 breast cancer cells (IC₅₀ = 25.13 ± 1.6 µg/mL). These results highlight the potential of U. urens EAE as a promising source of natural antioxidant and anticancer compounds.